Angioplasty has proved to be an effective treatment for vascular obstruction. After initial success, however, restenosis occurs at many angioplasty sites, leading to further treatment, health care expenses and human suffering. A critical need exists to prolong the patency of angioplasty sites. The goal of the proposed work is to test a novel therapeutic agent in the rapid and local dilation of angioplasty sites beyond the diameter of the balloon itself. This proposal describes key proof-of-concept studies investigating the efficacy and safety of the therapeutic agent. The goals of the proposal are to demonstrate immediate and persistent gains in vessel lumen diameter with direct intramural treatment during angioplasty and to determine the effects of treatment on vessel tensile strength. Completion of the specific aims and-successful achievement of milestone criteria will allow the project to progress to Phase II, which will consist of pre-clinical studies with the goal of submitting an Investigational New Drug application. In Phase III, clinical studies will be undertaken with the ultimate goal of commercializing a new therapeutic agent to prevent restenosis and occlusion following angioplasty, improving patient quality of life and reducing public health care burdens.